Effects of Administration Route, Dietary Condition, and Blood Glucose Level on Kinetics and Uptake of ^sup 18^F-FDG in Mice

摘要

The effects of dietary condition and blood glucose level on the kinetics and uptake of ^sup 18^F-FDG in mice were systematically investigated using intraperitoneal and tail-vein injection. Methods: Dynamic PET was performed for 60 min on 23 isoflurane-anesthetized male C57BL/6 mice after intravenous (n = 11) or intraperitoneal (n = 12) injection of ^sup 18^F-FDG. Five and 6 mice in the intravenous and intraperitoneal groups, respectively, were kept fasting overnight (18 ± 2 h), and the others were fed ad libitum. Serial blood samples were collected from the femoral artery to measure ^sup 18^F-FDG and glucose concentrations. Image data were reconstructed using filtered backprojection with CT-based attenuation correction. The standardized uptake value (SUV) was estimated from the 45- to 60-min image. The metabolic rate of glucose (MRGlu) and ^sup 18^F-FDG uptake constant (K^sub i^) were derived by Patlak graphical analysis. Results: In the brain, SUV and K^sub i^ were significantly higher in fasting mice with intraperitoneal injection, but MRGlu did not differ significantly under different dietary states and administration routes. Cerebral K^sub i^ was inversely related to elevated blood glucose levels, irrespective of administration route or dietary state. In myocardium, SUV, K^sub i^, and MRGlu were significantly lower in fasting than in nonfasting mice for both routes of injection. Myocardial SUV and K^sub i^ were strongly dependent on the dietary state, and K^sub i^ did not correlate with the blood glucose level. Similar results were obtained for skeletal muscle, although the differences were not as pronounced. Conclusion: Intraperitoneal injection is a valid alternative route, providing pharmacokinetic data equivalent to data from tail-vein injection for small-animal ^sup 18^F-FDG PET. Cerebral K^sub i^ varies inversely with blood glucose level, but the measured cerebral MRGlu does not correlate with blood glucose level or dietary condition. Conversely, the K^sub i^ values of the myocardium and skeletal muscle are strongly dependent on dietary condition but not on blood glucose level. In tissue in which ^sup 18^F-FDG uptake declines with increasing blood glucose, correction for blood glucose level will make SUV a more robust outcome measure of MRGlu. [PUBLICATION ABSTRACT] Show less